Growth factors mediate the processes by which a multicellular organism repairs various forms of damage to its integrity. Included in these processes are wound repair, for example skin closure after cuts or punctures, and compensatory growth, for example regrowth of function of certain organs to restore the original level of function and size after damage caused by mechanical or chemical means. The factors are necessary to the growth and differentiation of the cells that replace the destroyed or damaged tissue. Numerous active factors have been identified, based on the ability of tissue extracts containing the factors to stimulate the proliferation and differentiation of certain cultured cell lines.
Fibroblast growth factors (FGFs) appear to be specifically involved in mediating wound repair processes. They are angiogenic, hormone-like proteins that, among other things, stimulate the proliferation and induce or delay the differentiation of endothelial cells, which form the organism's blood vessels. See Patt et al., Kidney International 23:603-610 (1983). For a review of the role of growth factors generally in wound healing see ten Dijke, Biotechnology 7:793-97(Aug. 1989).
Two members of the FGF family, acidic and basic FGF (aFGF and bFGF), were originally delineated and have been the subject of extensive research. See, for example, Thomas, FASEB 434-40 (1987); Gospodarowicz et al., J. Cell. Phys. Supp. 5:15-26 (1987) and PCT publication WO 87/01728, published Mar. 26, 1987. Recently five additional putative members have been identified: FGF-5, see Zhan et al., Mol. and Cell. Biol. 8(8):3487-95(1988); FGF.6., see Marics, Oncogene 4:335-40(1989); Int-2, see Moore et al., EMBO J. 5(5):919-24(1986) and Dickson et al., Nature 26:833(1987); KGF; see Finch et al., Science 245:752-55(1989); and K-FGF see Delli Bovi et al., Cell 50:729-37(1987) and Taira et al., Proc. Natl. Acad. Sci. USA 84:2980-84(1987).